title: Synthesis and biological evaluation of 4-styrylcoumarin derivatives as inhibitors of TNF-α and IL-6 with anti-tubercular activity.
abstract: A series of 4-styrylcoumarin have been synthesized by Knoevenagel condensation between substituted 4-methylcoumarin-3-carbonitrile and different heterocyclic or aromatic aldehydes. 4-Methylcoumarin-3-carbonitrile has been synthesized by the base catalyzed reaction between substituted 2-hydroxyacetophenone and ethyl cyanoacetate. The structures of the newly synthesized compounds were confirmed by (1)H NMR, IR and mass spectral analysis. All the compounds were evaluated for their anti-inflammatory activity (against TNF-α and IL-6) and anti-tubercular activity. Compounds 6a, 6h and 6j exhibited promising activity against IL-6 with 72-87% inhibition and compound 6v showed potent activity against TNF-α with 73% inhibition at 10 μM concentration. Whereas compounds 6n, 6o, 6r and 6u showed very good anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain at <6.25 μM.
authors.affiliation: R&D Centre, Torrent Research Centre, Ahmedabad 380 009, Gujarat, India.
authors.forename: Kuldip
authors.initials: K
authors.lastname: Upadhyay
authors.forename: Abhay
authors.initials: A
authors.lastname: Bavishi
authors.forename: Shailesh
authors.initials: S
authors.lastname: Thakrar
authors.forename: Ashish
authors.initials: A
authors.lastname: Radadiya
authors.forename: Hardevsinh
authors.initials: H
authors.lastname: Vala
authors.forename: Shrey
authors.initials: S
authors.lastname: Parekh
authors.forename: Dhairya
authors.initials: D
authors.lastname: Bhavsar
authors.forename: Mahesh
authors.initials: M
authors.lastname: Savant
authors.forename: Manisha
authors.initials: M
authors.lastname: Parmar
authors.forename: Priti
authors.initials: P
authors.lastname: Adlakha
authors.forename: Anamik
authors.initials: A
authors.lastname: Shah
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003374:Coumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D000995:Antitubercular Agents; D003374:Coumarins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C030123:coumarin